Autoimmune diseases and adverse pregnancy outcomes: an umbrella review.

BACKGROUND: There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area. METHODS: Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported. RESULTS: Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren's syndrome RR 8.85 (95% CI 3.10-25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10-7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08-5.71) and SLE OR 3.20 (2.54-4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47-5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21-4.53) and coeliac disease OR 1.71 (1.36-2.14). Preterm birth was associated with T1DM OR 4.36 (3.72-5.12) and SLE OR 2.79 (2.07-3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54-7.80) and OR 3.80 (2.16-6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44-4.58), IBD OR 1.57 (1.03-2.38), and coeliac disease OR 1.57 (1.17-2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56-0.83). CONCLUSIONS: Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.

Association between pregnancy-related complications and development of type 2 diabetes and hypertension in women: an umbrella review.

BACKGROUND: Despite many systematic reviews and meta-analyses examining the associations of pregnancy complications with risk of type 2 diabetes mellitus (T2DM) and hypertension, previous umbrella reviews have only examined a single pregnancy complication. Here we have synthesised evidence from systematic reviews and meta-analyses on the associations of a wide range of pregnancy-related complications with risk of developing T2DM and hypertension. METHODS: Medline, Embase and Cochrane Database of Systematic Reviews were searched from inception until 26 September 2022 for systematic reviews and meta-analysis examining the association between pregnancy complications and risk of T2DM and hypertension. Screening of articles, data extraction and quality appraisal (AMSTAR2) were conducted independently by two reviewers using Covidence software. Data were extracted for studies that examined the risk of T2DM and hypertension in pregnant women with the pregnancy complication compared to pregnant women without the pregnancy complication. Summary estimates of each review were presented using tables, forest plots and narrative synthesis and reported following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines. RESULTS: Ten systematic reviews were included. Two pregnancy complications were identified. Gestational diabetes mellitus (GDM): One review showed GDM was associated with a 10-fold higher risk of T2DM at least 1 year after pregnancy (relative risk (RR) 9.51 (95% confidence interval (CI) 7.14 to 12.67) and although the association differed by ethnicity (white: RR 16.28 (95% CI 15.01 to 17.66), non-white: RR 10.38 (95% CI 4.61 to 23.39), mixed: RR 8.31 (95% CI 5.44 to 12.69)), the between subgroups difference were not statistically significant at 5% significance level. Another review showed GDM was associated with higher mean blood pressure at least 3 months postpartum (mean difference in systolic blood pressure: 2.57 (95% CI 1.74 to 3.40) mmHg and mean difference in diastolic blood pressure: 1.89 (95% CI 1.32 to 2.46) mmHg). Hypertensive disorders of pregnancy (HDP): Three reviews showed women with a history of HDP were 3 to 6 times more likely to develop hypertension at least 6 weeks after pregnancy compared to women without HDP (meta-analysis with largest number of studies: odds ratio (OR) 4.33 (3.51 to 5.33)) and one review reported a higher rate of T2DM after HDP (hazard ratio (HR) 2.24 (1.95 to 2.58)) at least a year after pregnancy. One of the three reviews and five other reviews reported women with a history of preeclampsia were 3 to 7 times more likely to develop hypertension at least 6 weeks postpartum (meta-analysis with the largest number of studies: OR 3.90 (3.16 to 4.82) with one of these reviews reporting the association was greatest in women from Asia (Asia: OR 7.54 (95% CI 2.49 to 22.81), Europe: OR 2.19 (95% CI 0.30 to 16.02), North and South America: OR 3.32 (95% CI 1.26 to 8.74)). CONCLUSIONS: GDM and HDP are associated with a greater risk of developing T2DM and hypertension. Common confounders adjusted for across the included studies in the reviews were maternal age, body mass index (BMI), socioeconomic status, smoking status, pre-pregnancy and current BMI, parity, family history of T2DM or cardiovascular disease, ethnicity, and time of delivery. Further research is needed to evaluate the value of embedding these pregnancy complications as part of assessment for future risk of T2DM and chronic hypertension.

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.

INTRODUCTION: Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy. METHODS AND ANALYSIS: Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

Association of pregnancy complications/risk factors with the development of future long-term health conditions in women: overarching protocol for umbrella reviews.

INTRODUCTION: With good medical care, most pregnancy complications like pre-eclampsia, gestational diabetes, etc resolve after childbirth. However, pregnancy complications are known to be associated with an increased risk of new long-term health conditions for women later in life, such as cardiovascular disease. These umbrella reviews aim to summarise systematic reviews evaluating the association between pregnancy complications and five groups of long-term health conditions: autoimmune conditions, cancers, functional disorders, mental health conditions and metabolic health conditions (diabetes and hypertension). METHODS AND ANALYSIS: We will conduct searches in Medline, Embase and the Cochrane database of systematic reviews without any language restrictions. We will include systematic reviews with or without meta-analyses that studied the association between pregnancy complications and the future risk of the five groups of long-term health conditions in women. Pregnancy complications were identified from existing core outcome sets for pregnancy and after consultation with experts. Two reviewers will independently screen the articles. Data will be synthesised with both narrative and quantitative methods. Where a meta-analysis has been carried out, we will report the combined effect size from individual studies. For binary data, pooled ORs with 95% CIs will be presented. For continuous data, we will use the mean difference with 95% CIs. The findings will be presented in forest plots to assess heterogeneity. The methodological quality of the studies will be evaluated with the AMSTAR 2 tool or the Cochrane risk of bias tool. The corrected covered area method will be used to assess the impact of overlap in reviews. The findings will be used to inform the design of prediction models, which will predict the risk of women developing these five group of health conditions following a pregnancy complication. ETHICS AND DISSEMINATION: No ethical approvals required. Findings will be disseminated through publications in peer-reviewed journals and conference presentations.